Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

BACKGROUND: Among patients with resected, epidermal growth factor receptor (EGFR)-mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival. METHODS: In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met. The primary end point was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary end points included disease-free survival among patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: Of 682 patients who underwent randomization, 339 received osimertinib and 343 received placebo. Among patients with stage II to IIIA disease, the 5-year overall survival was 85% in the osimertinib group and 73% in the placebo group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI], 0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to IIIA disease), the 5-year overall survival was 88% in the osimertinib group and 78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34 to 0.70; P<0.001). One new serious adverse event, pneumonia related to coronavirus disease 2019, was reported after the previously published data-cutoff date (the event was not considered by the investigator to be related to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had a safety profile consistent with that in the primary analysis. CONCLUSIONS: Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).

Risk factors associated with indoor transmission during home quarantine of COVID-19 patients.

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves. Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p = 0.018). Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.

Physical Therapy for Adults with Heart Failure.

Heart failure (HF) is a complex clinical syndrome caused by structural and/or functional abnormalities that results in significant disease burdens not only to the patients and their families but also to the society. Common symptoms/signs of HF include dyspnea, fatigue, and exercise intolerance, which significantly reduce the quality of life of individuals. Since the coronavirus disease 2019 (COVID-19) pandemic in 2019, it has been found that individuals with cardiovascular disease are more vulnerable to COVID-19-related cardiac sequelae including HF. In this article, we review the updated diagnosis, classifications, and interventional guidelines of HF. We also discuss the link between COVID-19 and HF. The latest evidence about physical therapy for patients with HF in both the stable chronic phase and acute cardiac decompensation phase is reviewed. Physical therapy for HF patients with circulatory support devices is also described.

A Review of the Current Trends Related to Educational Leadership Research in the U.S

Leadership has been an important force leading the progress of human society throughout history. High-quality educational leaders are essential to the continuous improvement of educational development. Scholars and practitioners have been primarily concerned with educational leadership research after the 1970s effective school movement. The topic of educational leadership research has also been innovated during the COVID-19 pandemic. This paper summarized research trends in educational leadership as the following: (1) equity-oriented leadership research;(2) learning-centered leadership research;(3) high-quality school leadership research;(4) COVID-19 emerging educational leadership research topic. It will serve as a guideline for the direction of educational leadership research in Taiwan.

Immunogenicity of a spike protein subunit-based COVID-19 vaccine with broad protection against various SARS-CoV-2 variants in animal studies.

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic.

The expression of respiratory tract virus in pediatric glomerular disease: a retrospective study of 45 renal biopsy in China.

BACKGROUND: More attention has been put on the relationship between pediatric glomerular disease and respiratory tract virus infection. Children with glomerular illness, however, are uncommonly found to have biopsy-proven pathological evidence of viral infection. The purpose of this study is to determine whether and what kind of respiratory viruses are found in renal biopsy from glomerular disorders. METHODS: We used a multiplex PCR to identify a wide range of respiratory tract viruses in the renal biopsy samples (n = 45) from children with glomerular disorders and a specific PCR to verify their expression. RESULTS: These case series included 45 of 47 renal biopsy specimens, with 37.8% of male and 62.2% of female patients. Indications for a kidney biopsy were present in all of the individuals. In 80% of the samples, respiratory syncytial virus was discovered. Following that, the RSV subtypes in several pediatric renal disorders were found. There were 16 RSVA positives, 5 RSVB positives, and 15 RSVA/B positives, accounting for 44.4%, 13.9%, and 41.7%, respectively. Nephrotic syndrome samples made up 62.5% of RSVA positive specimens. The RSVA/B-positive was detected in all pathological histological types. CONCLUSIONS: Patients with glomerular disease exhibit respiratory tract viral expression in the renal tissues, especially respiratory syncytial virus. This research offers new information on the detection of respiratory tract viruses in renal tissue, which may facilitate the identification and treatment of pediatric glomerular diseases.

Clinical application of ABO blood typing.

BACKGROUND: The ABO blood group is closely related to clinical blood transfusion, transplantation, and neonatal hemolytic disease. It is also the most clinically significant blood group system in clinical blood transfusion. OBJECTIVE: The purpose of this paper is to review and analyze the clinical application of the ABO blood group. METHODS: The most common ABO blood group typing methods in clinical laboratories are hemagglutination test and microcolumn gel test, while genotype detection is mainly adopted in clinical identification of suspicious blood types. However, in some cases, the expression variation or absence of blood type antigens or antibodies, experimental techniques, physiology, disease, and other factors affect the accurate determination of blood types, which may lead to serious transfusion reactions. RESULTS: The mistakes could be reduced or even eliminated by strengthening training, selecting reasonable identification methods, and optimizing processes, thereby improving the overall identification level of the ABO blood group. ABO blood groups are also correlated with many diseases, such as COVID-19 and malignant tumors. Rh blood groups are determined by the RHD and RHCE homologous genes on chromosome 1 and are classified as Rh negative or positive according to the D antigen., the agglutination method is often used in clinical settings, while genetic and sequencing methods are often used in scientific research. CONCLUSION: Accurate ABO blood typing is a critical requirement for the safety and effectiveness of blood transfusion in clinical practice. Most studies were designed for investigating rare Rh blood group family, and there is a lack of research on the relationship between Rh blood groups and common diseases.

Demographics, employment, and proximity to covid-19 as predictors of preparedness among Taiwanese health social workers.

COVID-19 struck the world violently and cause negative psychological consequences on health professionals. The preparedness of social workers for the pandemic is critical while facing these challenges and pressures. The study aimed to explore what are the roles of demographic, employment, and proximity to Covid-19 in predicting preparedness for the next wave of COVID among social workers in Taiwan. A total of 158 participants were conveniently sampled and multiple regression, univariate analysis, and two-way ANOVA were conducted. The results demonstrated that the demographic and employment variables significantly predicted preparedness, and there were significant differences among demographics on preparedness and an interaction effect between seniority and age. Consequently, middle-aged social workers with junior seniority years may have more difficulties in their preparation for the current situation. The implication of our findings is also discussed.

Platelet Activation and Cytokine Release of Interleukin-8 and Interferon-Gamma-Induced Protein 10 after ChAdOx1 nCoV-19 Coronavirus Vaccine Injection.

Coronavirus disease 2019 (COVID-19) vaccines are associated with serious thromboembolic or thrombocytopenic events including vaccine-induced immune thrombocytopenia and thrombosis and immune thrombocytopenia, particularly AZD1222/ChAdOx1. According to the proposed mechanism, COVID-19 vaccines stimulate inflammation and platelet activation. In this study, we analyzed the role of AZD1222/ChAdOx1 vaccines in the activation of platelets and the release of anti-PF4 antibodies and inflammatory cytokines in a cohort of healthy donors without vaccine-induced immune thrombotic thrombocytopenia (VITT). Forty-eight healthy volunteers were enrolled in this study. Blood samples were collected from peripheral blood at three time points: before vaccination and 1 and 7 days after vaccination. Compared with the prevaccination data, a decrease in the leukocyte and platelet counts was observed 1 day after vaccination, which recovered 7 days after injection. The percentage of activated GPIIb/IIIa complex (PAC-1) under high ADP or thrombin receptor-activating peptide stimulation increased 1 day after vaccination. Furthermore, interluekin-8 (IL-8) and interferon-gamma-induced protein 10 (IP-10) increased significantly. Additionally, platelet activation and inflammation, with the release of cytokines, were observed; however, none of the individuals developed VITT. Mild thrombocytopenia with platelet activation and inflammation with an elevation of IL-8 and IP-10 were observed after AZ vaccination.

virDTL: Viral Recombination Analysis Through Phylogenetic Reconciliation and Its Application to Sarbecoviruses and SARS-CoV-2.

An accurate understanding of the evolutionary history of rapidly-evolving viruses like SARS-CoV-2, responsible for the COVID-19 pandemic, is crucial to tracking and preventing the spread of emerging pathogens. However, viruses undergo frequent recombination, which makes it difficult to trace their evolutionary history using traditional phylogenetic methods. In this study, we present a phylogenetic workflow, virDTL, for analyzing viral evolution in the presence of recombination. Our approach leverages reconciliation methods developed for inferring horizontal gene transfer in prokaryotes and, compared to existing tools, is uniquely able to identify ancestral recombinations while accounting for several sources of inference uncertainty, including in the construction of a strain tree, estimation and rooting of gene family trees, and reconciliation itself. We apply this workflow to the Sarbecovirus subgenus and demonstrate how a principled analysis of predicted recombination gives insight into the evolution of SARS-CoV-2. In addition to providing confirming evidence for the horseshoe bat as its zoonotic origin, we identify several ancestral recombination events that merit further study.

Deep Learning for Detecting COVID-19 Using Medical Images.

The global spread of COVID-19 (also known as SARS-CoV-2) is a major international public health crisis [...].

Structural basis for a conserved neutralization epitope on the receptor-binding domain of SARS-CoV-2.

Antibody-mediated immunity plays a crucial role in protection against SARS-CoV-2 infection. We isolated a panel of neutralizing anti-receptor-binding domain (RBD) antibodies elicited upon natural infection and vaccination and showed that they recognize an immunogenic patch on the internal surface of the core RBD, which faces inwards and is hidden in the "down" state. These antibodies broadly neutralize wild type (Wuhan-Hu-1) SARS-CoV-2, Beta and Delta variants and some are effective against other sarbecoviruses. We observed a continuum of partially overlapping antibody epitopes from lower to upper part of the inner face of the RBD and some antibodies extend towards the receptor-binding motif. The majority of antibodies are substantially compromised by three mutational hotspots (S371L/F, S373P and S375F) in the lower part of the Omicron BA.1, BA.2 and BA.4/5 RBD. By contrast, antibody IY-2A induces a partial unfolding of this variable region and interacts with a conserved conformational epitope to tolerate all antigenic variations and neutralize diverse sarbecoviruses as well. This finding establishes that antibody recognition is not limited to the normal surface structures on the RBD. In conclusion, the delineation of functionally and structurally conserved RBD epitopes highlights potential vaccine and therapeutic candidates for COVID-19.

Country- and app-level factors affecting the adoption and evaluation of COVID-19 mobile apps.

BACKGROUND: Countries across the globe have released many COVID-19 mobile apps. However, there is a lack of systematic empirical investigation into the factors affecting the adoption and evaluation of COVID-related apps. This study explores what factors at the country level and the app levels would influence the adoption and evaluation of COVID-19 apps. METHODS: We collected data on 267 COVID-19 apps in App Store and Google Play. The number of installs, ratings, reviews and rating scores were used as indicators of adoption and evaluation. Country-level predictors include the number of infected cases and the political system (i.e., democratic vs. non-democratic). App-level predictors include developer (i.e., government vs. non-government) and functions. Four app functions were coded for analysis: providing health information, contact tracing, home monitoring, and consultation. Negative binomial regression and OLS (Ordinary Least Square) regression were used to analyze the data. RESULTS: Our analyses show that apps developed by countries with more infected cases (B = 0.079, CI (Confidence Interval) = 0.000, 0.158; P = .049) and by non-governmental institutions (B=-0.369, CI=-0.653, -0.083; P = .01) received more positive rating scores. Apps with home monitoring function received lower rating scores (B=-0.550, CI=-0.971, -0.129; P = .01). Regarding adoption, apps developed by governments were more likely to be installed (IRR (Incident Rate Ratio) = 8.156, CI = 3.389, 19.626; P < .001), to be rated (IRR = 26.036, CI = 7.331, 92.468; P < .001), and to receive user comments (IRR = 12.080, CI = 3.954, 37.568; p < .001). Apps with functions of contact tracing or consultation were more likely to be installed (IRR = 4.533, CI = 2.072, 9.918; p < .001; IRR = 4.885, CI = 1.970, 12.111; p < .001), to be rated (IRR = 11.634, CI = 3.486, 38.827; p < .001; IRR = 17.194, CI = 5.309, 55.680; p < .001), and to receive user comments (IRR = 5.688, CI = 2.052, 5.770; p < .001; IRR = 16.718, CI = 5.363, 52.113; p < .001). Apps with home monitoring functions were less likely to be rated (IRR = 0.206, CI = 0.047, 0.896; P = .04) but more likely to receive user comments (IRR = 3.874, CI = 1.044, 14.349; P = .04). Further analysis shows that apps developed in democratic countries (OR (Odd Ratio) = 3.650, CI = 1.238, 10.758; P = .02) or by governments (OR = 7.987, CI = 4.106, 15.534, P < .001) were more likely to include the function of contact tracing. CONCLUSION: This study systematically investigates factors affecting the adoption and evaluation of COVID-19 apps. Evidence shows that government-developed apps and the inclusion of contact tracing and consultation app functions strongly predict app adoption.

The Relationship Between Personality Traits and Clinical Decision-Making, Anxiety and Stress Among Intern Nursing Students During COVID-19: A Cross-Sectional Study.

Purpose: The aim of this study was to investigate whether the personality traits of intern nursing students could serve as valid predictors of their psychological status and clinical decision making. Additionally, we aimed to understand the psychological state of intern nursing students during the regular epidemic prevention and control stage of COVID-19. Participants and Methods: This study was designed as a cross-sectional survey. A total of 181 intern nursing students involved in clinical placements participated in this study. Participants provided relevant data by completing the Big Five Inventory-44, the Self-Rating Anxiety Scale, the Perceived Stress Scale 14, and the Clinical Decision-Making in Nursing Scale. Results: The results showed that neuroticism (ß = -0.282, p < 0.01) and openness (ß = 0.302, p < 0.001) played significant roles in predicting clinical decision-making skills among intern nursing students. Regression analysis also showed extraversion (ß = -0.249, p < 0.01), openness (ß = 0.2, p < 0.01), and neuroticism (ß = 0.391, p < 0.001) could significantly predict stress in intern nursing students. The agreeableness (ß = -0.354, p < 0.001) and neuroticism (ß = 0.237, p < 0.01) could also predict the anxiety of intern nursing students. Additionally, some intern nursing students still suffered from anxiety and stress in the context of the ongoing pandemic. Conclusion: Personality traits are good predictors of clinical decision-making, anxiety and stress among intern nursing students. In conclusion, the openness in personality traits of intern nursing students should be valued and cultivated in clinical work, which will benefit the development of nursing talents.

Machine learning identifies a COVID-19-specific phenotype in university students using a mental health app (preprint)

Advances in smartphone technology have allowed people to access mental healthcare via digital apps from wherever and whenever they choose. University students experience a high burden of mental health concerns. Although these apps improve mental health symptoms, user engagement has remained low. Studies have shown that users can be subgrouped based on unique characteristics that just-in-time adaptive interventions (JITAIs) can use to improve engagement. To date, however, no studies have examined the effect of the COVID-19 pandemic on these subgroups. Here, we use machine learning to examine user subgroup characteristics across three COVID-19-specific timepoints: during lockdown, immediately following lockdown, and three months after lockdown ended. We demonstrate that there are three unique subgroups of university students who access mental health apps. Two of these, with either higher or lower mental well-being, were defined by characteristics that were stable across COVID-19 timepoints. The third, situational well-being, had characteristics that were timepoint-dependent, suggesting that they are highly influenced by traumatic stressors and stressful situations. This subgroup also showed feelings and behaviours consistent with burnout. Overall, our findings clearly suggest that user subgroups are unique: they have different characteristics and therefore likely have different mental healthcare goals. Our findings also highlight the importance of including questions and additional interventions targeting traumatic stress(ors), reason(s) for use, and burnout in JITAI-style mental health apps to improve engagement.

In situ structure and dynamics of an alphacoronavirus spike protein by cryo-ET and cryo-EM

Porcine epidemic diarrhea (PED) is a highly contagious swine disease caused by porcine epidemic diarrhea virus (PEDV). PED causes enteric disorders with an exceptionally high fatality in neonates, bringing substantial economic losses in the pork industry. The trimeric spike (S) glycoprotein of PEDV is responsible for virus-host recognition, membrane fusion, and is the main target for vaccine development and antigenic analysis. The atomic structures of the recombinant PEDV S proteins of two different strains have been reported, but they reveal distinct N-terminal domain 0 (D0) architectures that may correspond to different functional states. The existence of the D0 is a unique feature of alphacoronavirus. Here we combined cryo-electron tomography (cryo-ET) and cryo-electron microscopy (cryo-EM) to demonstrate in situ the asynchronous S protein D0 motions on intact viral particles of a highly virulent PEDV Pintung 52 strain. We further determined the cryo-EM structure of the recombinant S protein derived from a porcine cell line, which revealed additional domain motions likely associated with receptor binding. By integrating mass spectrometry and cryo-EM, we delineated the complex compositions and spatial distribution of the PEDV S protein N-glycans, and demonstrated the functional role of a key N-glycan in modulating the D0 conformation. Hsu and co-workers integrate cryo-electron tomography, cryo-electron microscopy and mass spectrometry to reveal the structural polymorphism of a pig coronavirus spike protein within intact viral particles, and how glycosylation modulates the conformational changes pertinent to host recognition.

Changes in lifestyles and depressive symptom among patients with chronic diseases during COVID-19 lockdown.

This study aims to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among patients with NCDs (noncommunicable diseases). We incorporated a COVID-19 survey to the WELL China cohort, a prospective cohort study with the baseline survey conducted 8-16 months before the COVID-19 outbreak in Hangzhou, China. The COVID-19 survey was carried out to collect information on lifestyle and depressive symptom during lockdown. A total of 3327 participants were included in the COVID-19 survey, including 2098 (63.1%) reported having NCDs at baseline and 1457 (44%) without NCDs. The prevalence of current drinkers decreased from 42.9% before COVID-19 lockdown to 23.7% during lockdown, current smokers from 15.9 to 13.5%, and poor sleepers from 23.9 to 15.3%, while low physical activity increased from 13.4 to 25.2%, among participants with NCDs (P < 0.05 for all comparisons using McNemar's test). Participants with NCDs were more likely than those without to have depressive symptom (OR, 1.30; 95% CI 1.05-1.61), especially among those who need to refill their medication during the COVID-19 lockdown (OR, 1.52; 95% CI 1.15-2.02). Our findings provide insight into the development of targeted interventions to better prepare patients with NCDs and healthcare system to meet the challenge of future pandemic and lockdown.